Tandem reaction – Stereoselective Synthesis of Pyrrolizidines

I recently found this paper in the last issue of the Angewandte. No total synthesis this time but a very interesting methodology and a complex mechanism. The main step looks like this:

While trying to figure out the mechanism by myself with the aid of the published one, I was wondering why they found an acyl shift there… So here’s my version of the mechanism. It is roughly the same except the mentioned acyl shift which I could not figure out using their intermediates. All in all the stereochemistry remains the same but there is probably a fault in the relative configuration which would result in the reverse stereochemistry. I worked the mechanism step by step out and maybe you find some faults in my one. So here it is:

It starts with a Michael addition of ethyl isocyanoacetate catalysed by 30 mol% of DBU onto the most activated double bond. After tautomerism and another proton abstraction the second Michael addition occurred leading to intermediate I.

Then the tautomeric enolate attacks the isocyanide which results after protonation in the intermediate II. Then a Baylis-Hillman like reaction occurred when the formed iminium ion attacks the carbonyl moiety to give the tetracyclic, bridged intermediate III. This one then collapses to give the product.

The proposed mechanism involves the breaking of a C-N bond and an acyl shift in intermediate which I found illogical to form the product. The published mechanism is summed up to 6 steps so presumably they don’t feel certain with it too.

All in all a cool reaction. The yields are great and the stereoselectivity is excellent.

I would be pleased if someone who read this article too would correct or confirm my ideas or maybe post a third one. I’m really interested in good suggestions so have your say.